2-Ethoxy-4,6-dihydroxypyrimidine (DHEP) having the Formula (I): ##STR1## has been found to be a particularly useful intermediate for the synthesis of certain valuable herbicides used for the control of weeds in agronomic crops, such as ethoxy substituted 1,2,4-triazolo[1,5-c]pyrimidine-2-sulfonamides, as disclosed in U.S. Pat. No. 5,010,195 (Van Heertum et al.). DHEP or its monosodium salt can be converted to a 4,6-dihalo-2-ethoxypyrimidine by treating the DHEP with a phosphorus oxyhalide compound, such as phosphorus oxychloride. Then, the 4,6-dihalo-2-ethoxypyrimidine can be treated with hydrazine hydrate and triethylamine to form a 2-ethoxy-6-halo-4-hydrazinopyrimidine compound. The latter reaction can be carried out in water or in an organic solvent, such as acetonitrile, at a temperature of between about 0.degree. C. and 40.degree. C. using a slight excess of hydrazine hydrate. The 2-ethoxy-6-halo-4-hydrazinopyrimidine compound can, if desired, be recovered by adding water to promote precipitation and then recovering the precipitate by filtration, centrifugation, or extraction. The above-referenced U.S. Pat. No. 5,010,195, which is incorporated in its entirety herein by reference, teaches how to make useful herbicide compounds from 2-ethoxy-6-halo-4-hydrazinopyrimidine compounds.
One method taught in the art for making the 2-methoxy analog of DHEP is disclosed by S. Basterfield and E. C. Powell in Canadian Journal of Research, vol. 1, pp. 261-272 (1929). In this article, Basterfield and Powell describe the synthesis of a number of 2-alkoxypyrimidine derivatives, including 2-methoxy-4,6-dihydroxypyrimidine (DHMP). DHMP is prepared by condensing O-methylisourea with dimethyl malonate. Although a 75% of theoretical yield is reported in the article, the theoretical yield requires consumption of 2 equivalents of O-methylisourea to form 1 equivalent of the O-methylisourea salt of DHMP. Thus, the reported 75% yield means that 0.75 moles of DHMP salt are formed for every 2 moles of O-methylisourea utilized. The O-methylisourea is prepared by first preparing and isolating the hydrochloride salt of O-methylisourea, then neutralizing this salt with potassium hydroxide in ether to form neutral O-methylisourea, which is apparently isolated as well. At page 262 of their article, Basterfield and Powell reference the unpublished observations of Stieglitz and Basterfield, who found that O-ethylisourea can be condensed with dimethyl malonate in the absence of a base and of a solvent to obtain the O-ethylisourea salt of 2-ethoxybarbituric acid, i.e., a salt of DHEP.
A second method for making DHMP is disclosed by C. J. Moye in Australian Journal of Chemistry, vol. 17, pp. 1309-1310 (1964). Moye teaches condensing O-methylisourea hydrogen methyl sulfate with diethyl malonate in a methanol solvent to make DHMP. Three equivalents of sodium methoxide are used as a base to effect the condensation (two equivalents are necessary to neutralize the O-methylisourea salt and one equivalent is used to drive the condensation reaction). The methanol and sodium methoxide have the same methoxy moiety as the O-methylisourea compound and the desired product (DHMP).